Association between type 2 diabetes mellitus-related SNP variants and obesity traits in a Saudi population
Obesity, commonly measured as body mass index (BMI), has been on a rapid rise around the world and is an underlying cause of several chronic non-communicable diseases, including type 2 diabetes mellitus (T2DM). In addition to the environmental factors, genetic factors may also contribute to the ongoing obesity epidemic in Saudi Arabia. This study investigated the association between variants of 36 previously established T2DM SNPs and obesity phenotypes in a population of Saudi subjects. Study subjects consisted of 975 obese (BMI: ≥30), 825 overweight (25–30) and 423 lean controls (18–25) and of these 927 had a history of T2DM. Subjects were genotyped for 36 SNPs, which have been previously proved to be T2DM linked, using the KASPar method and the means of BMI and waist circumference (WC) corresponding to each of the genotypes were compared by additive, recessive and dominant genetic models. Five and seven of 36 T2DM-related SNPs were significantly associated with the BMI and WC, respectively. Variants of SNPs rs7903146, rs1552224 and rs11642841 in the control group and rs7903146 in T2DM group showed significant association with both BMI and WC. Variant of SNP rs10440833 was significantly associated with BMI in T2DM group of both males [OR = 1.8 (1.0, 3.3); P = 0.04] and females [OR = 2.0 (1.0, 3.9); P = 0.04]. Genetic risk scores explained 19 and 14 % of WC and hip size variance in this population. Variants of a number of established T2DM related SNPs were associated with obesity phenotypes and may be significant hereditary factors in the pathogenesis of T2DM.
KeywordsObesity SNP Type 2 diabetes BMI Waist circumference FTO GWA studies
This study was funded by the Biomarkers Research Program at King Saud University, Riyadh, Saudi Arabia. The authors are grateful to the primary care physicians and nurses of the PHCCs in Riyadh for patient recruitment and sample collection. The authors also thank Mr. Benjamin Vinodson for statistical analysis of the data.
Conflict of interest
The authors have nothing to disclose.
- 2.Dubois L, Ohm Kyvik K, Girard M, Tatone-Tokuda F, Perusse D, Hjelmborg J, Skytthe A, Rasmussen F, Wright MJ, Lichtenstein P et al (2012) Genetic and environmental contributions to weight, height, and BMI from birth to 19 years of age: an international study of over 12,000 twin pairs. PLoS ONE 7:e30153PubMedCentralPubMedCrossRefGoogle Scholar
- 15.Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, Hu T, de Bakker PI, Abecasis GR, Almgren P, Andersen G et al (2008) Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 40:638–645PubMedCentralPubMedCrossRefGoogle Scholar
- 23.Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894PubMedCentralPubMedCrossRefGoogle Scholar
- 24.Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I et al (2009) Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 41:18–24PubMedCrossRefGoogle Scholar
- 30.Liu PH, Chang YC, Jiang YD, Chen WJ, Chang TJ, Kuo SS, Lee KC, Hsiao PC, Chiu KC, Chuang LM (2009) Genetic variants of TCF7L2 are associated with insulin resistance and related metabolic phenotypes in Taiwanese adolescents and Caucasian young adults. J Clin Endocrinol Metab 94:3575–3582PubMedCrossRefGoogle Scholar
- 31.Palmer ND, Hester JM, An SS, Adeyemo A, Rotimi C, Langefeld CD, Freedman BI, Ng MC, Bowden DW (2011) Resequencing and analysis of variation in the TCF7L2 gene in African Americans suggests that SNP rs7903146 is the causal diabetes susceptibility variant. Diabetes 60:662–668PubMedCrossRefGoogle Scholar
- 37.Okamura T, Yanobu-Takanashi R, Takeuchi F, Isono M, Akiyama K, Shimizu Y, Goto M, Liang YQ, Yamamoto K, Katsuya T et al (2012) Deletion of CDKAL1 affects high-fat diet-induced fat accumulation and glucose-stimulated insulin secretion in mice, indicating relevance to diabetes. PLoS ONE 7:e49055PubMedCentralPubMedCrossRefGoogle Scholar